Nipah virus (NiV) and Hendra virus (HeV) are closely related emerging paramyxoviruses that comprise the Henipavirus genus (Anonymous 1999 MMWR Morb Mortal Wkly Rep Ward, J. W. ed. 48:335-337; Chew, M. H. et al. 2000 J Infect Dis 181:1760-1763; Chua, K. B. et al. 2000 Ann Neurol 48:802-805; Eaton, B. T. 2001 Microbes Infect 3:277-278; Goh, K. J. et al. 2000 N Engl J Med 342:1229-1235; Lee, K. E. et al. 1999 Ann Neurol 46:428-432; Lim, C. C. et al. 2000 Am J Neuroradiol 21:455-461; Murray, K. et al. 1995 Science 268:94-97). Paramyxoviruses are negative-sense RNA containing enveloped viruses and contain two major membrane-anchored envelope glycoproteins that are required for infection of a receptive host cell. All members contain an F glycoprotein which mediates pH-independent membrane fusion between the virus and its host cell, while the second attachment glycoprotein can be either a hemagglutinin-neuraminidase protein (HN), a hemagglutinin protein (H), or a G protein depending on the particular virus (reviewed in Lamb, R. A. and Kolakofsky, D. 2001 in Fields Virology, eds. Knippe, D. M. & Howley, P. M., Lippincott Williams & Wilkins, Philadelphia, pp. 1305-1340). As with all paramyxoviruses, these glycoproteins are also the principal antigens to which virtually all neutralizing antibodies are directed.
The broad species tropisms and the ability to cause fatal disease in both animals and humans distinguish HeV and NiV from all other known paramyxoviruses (reviewed in Eaton, B. T. 2001 Microbes Infect 3:277-278). They are Biological Safety Level-4 (BSL-4) pathogens, and are on the NIAID Biodefense research agenda as zoonotic emerging category C priority pathogens that could be used as bioterror agents. The henipaviruses can be amplified and cause disease in large animals and be aerosol transmitted to humans where disease can be a severe respiratory illness and febrile encephalitis. They can be readily grown in cell culture or embryonated chicken eggs, produce high un-concentrated titers (˜108 TCID50/ml; Crameri, G. et al. 2002 J Virol Methods 99:41-51), and are highly infectious (Field, H. et al. 2001 Microbes Infect 3:307-314; Hooper, P. et al. 2001 Microbes Infect 3:315-322).
NiV has recently re-emerged in Bangladesh. Two outbreaks of NiV in 2004 have been confirmed, and yet another one occurred in January of 2005 (Anonymous 2005 Communicable Disease Report Weekly (CDR Weekly) Vol. 15 No. 16). Several important observations in these most recent outbreaks have been made, including a higher incidence of acute respiratory distress syndrome, person-to-person transmission, and significantly higher case fatality rates (60-75%) than in Malaysia (about 40%) where the virus was discovered or suspected to have originated (Anonymous 2004 Wkly Epidemiol Rec 79:168-171; Anonymous 2004 Health and Science Bulletin (ICDDR,B) 2:5-9; Butler, D. 2004 Nature 429:7; Enserink, M. 2004 Science 303:1121; Hsu, V. P. et al. 2004 Emerg Infect Dis 10:2082-2087). Currently, no therapeutics for NiV or HeV-infected individuals are available, and a vaccine for prevention of disease in human or livestock populations does not exist. Although antibody responses were detected in infections caused by these viruses, human monoclonal antibodies (hmAbs) have not been identified against either virus. A number of studies have shown the importance of neutralizing antibodies in recovery and protection from viral infections (Dimitrov, D. S. 2004 Nat Rev Microbiol 2:109-122). Therefore, the development of neutralizing hmAbs against NiV and HeV could have important implications for prophylaxis and passive immunotherapy. In addition, the characterization of the epitopes of the neutralizing antibodies could provide helpful information for development of candidate vaccines and drugs. Finally, such antibodies could be used for diagnosis and as research reagents.